A novel murine model of cerebral scedosporiosis: lack of efficacy of amphotericin B

J Antimicrob Chemother. 2004 Dec;54(6):1092-5. doi: 10.1093/jac/dkh468. Epub 2004 Oct 27.


Objectives: Cerebral scedosporiosis is a life-threatening infection that is difficult to treat. The aim of this work was to develop a murine model of cerebral infection by Scedosporium apiospermum using intracranial inoculation and to use this model to evaluate the efficacy of amphotericin B deoxycholate and liposomal amphotericin B.

Methods: Mice were rendered neutropenic by intraperitoneal cyclophosphamide and intravenous (iv) 5-fluorouracil administration. Animals were infected with iv or intracranial inoculation of 1 x 10(4), 5 x 10(4) or 5 x 10(5) cfu of a clinical strain of S. apiospermum. Tissue burden reduction was determined in kidneys and brain 4 days after the infection. Efficacy of amphotericin B and liposomal amphotericin B (0.8 mg/kg/day intraperitoneally and 40 mg/kg/day iv, respectively) was evaluated in neutropenic mice infected iv or intracranially with 5 x 10(4) cfu. Survival was analysed with the log-rank test. Fungal burden values of different groups were compared using the Mann-Whitney U-test.

Results: In our model, intracranial infection produced a higher fungal load in the brain and a lower fungal load in the kidney than iv inoculation. Survival of animals infected intracranially and treated with amphotericin B or liposomal amphotericin B (mean survival time = 8.3 and 9.2 days, respectively) was not different from the control group (P=0.58 and 0.85, respectively).

Conclusions: We have developed a murine model of cerebral scedosporiosis, which may be useful for studying various pathological aspects of this infection and evaluating new therapeutic approaches. Amphotericin B and liposomal amphotericin B were unable to resolve the infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / therapeutic use*
  • Animals
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / therapeutic use*
  • Brain / microbiology
  • Brain / pathology
  • Brain Diseases / drug therapy*
  • Brain Diseases / microbiology
  • Brain Diseases / mortality
  • Brain Diseases / pathology
  • Disease Models, Animal*
  • Humans
  • Liposomes / administration & dosage
  • Liposomes / therapeutic use
  • Male
  • Mice
  • Mycetoma / drug therapy*
  • Mycetoma / microbiology
  • Mycetoma / mortality
  • Mycetoma / pathology
  • Neutropenia
  • Scedosporium / drug effects*
  • Scedosporium / pathogenicity
  • Treatment Failure


  • Antifungal Agents
  • Liposomes
  • Amphotericin B